Cette thèse concerne la comparaison des stratégies de coarticulation nasale sur les voyelles dans deux langues possédant des voyelles nasales phonologiques (français et ourdou) et trois langues ne possédant pas de voyelles nasales phonologiques (l’anglais américain, le bosnien et le norvégien). Pour évaluer le degré de nasalité produit, nous avons utilisé un accéléromètre piézoélectrique (AP) (non invasive et transportable). Cinq locuteurs natifs par langue ont enregistré un corpus de logatomes (CVNC et un ensemble de mots et de phrases. Cette thèse montre que (1) une différence inter-langues de stratégies existe, confirmant ainsi un fait déjà connu, (2) l’existence d’un contraste phonologique entre voyelles nasales et voyelles orales n’a pas d’influence prévisible sur la propagation de la nasalité, confirmant ainsi un fait déjà connu, (3) un modèle d’anticipation de nasalité peut être plus adéquat pour une langue que pour une autre, (4) les auditeurs francophones ne distinguent pas entre plusieurs degrés de nasalisation contextuelle, mais il existe une corrélation entre la quantité de vibrations issue de l’AP et la perception du degré de nasalisation pour les auditeurs de l’ourdou. L’intérêt de cette étude est que la comparaison de phénomènes de coarticulation nasale des voyelles dans les cinq langues a été faite avec la même instrumentation, dans les mêmes conditions. Un autre intérêt est de montrer l’intérêt de la méthode choisie. / This thesis concerns the comparison of the phenomena of nasal coarticulation of vowels in two languages that have phonological nasal vowels (French and Urdu) and three languages that don’t have phonological nasal vowels (American English, Bosnian and Norwegian). To evaluate the degree of nasality, we used a piezoelectric accelerometer (PA) (non invasive and transportable). Five native speakers of each language recorded the corpus of logatomes CVNC, words and sentences. This thesis shows that : (1) an inter-language difference exists with respect to nasal coarticulation strategies, confirming an already known fact, (2) the existence or absence of a phonological contrast between nasal vowels and oral vowels in a language does not necessarily have a predictable influence on the propagation of nasality, confirming an already known fact, (3) one model of anticipation of nasality may be more suitable for one language, while for another language another model may be more suitable. (4) the french auditors don’t disinguish between several degrees of contextual nasalization but there is a correlation between the quantity of vibration from the AP and the perception of the degree of nasality for the auditors of urdu. The interest of this study is that the comparison of the nasal coarticulation phenomena of vowels in the five languages was made with the same instrumentations under the same conditions. Another interest is to show the interest of the chosen method.

Introdução: A lavagem nasal com budesonida em solução salina de alto volume (BAV) tem sido utilizada no tratamento de rinossinusite crônica (RSC). Atualmente, não existem evidências de superioridade da BAV sobre o placebo (PLA). Objetivo: O estudo avalia a eficácia da lavagem nasal com BAV na RSC com polipose nasossinusal de difícil controle e asma brônquica. Métodos: Os indivíduos foram prospectivamente recrutados e randomizados em dois grupos: budesonida (1mg/dia) ou placebo, diluídos em 250mL de Soro Fisiológico a 0,9%, e orientados para aplicar 125mL dessa solução em cada narina de 12 em 12 horas, por 12 semanas. Os pacientes foram avaliados quanto a: qualidade de vida doença-específica (SNOT-20, NOSE), endoscopia nasossinusal (Lund-Kennedy) e olfato (UPSIT). Efeitos adversos foram avaliados por meio do cortisol sérico e urinário, feita a avaliação da opacidade do cristalino e teste de sobrecarga hídrica para aferição da pressão ocular. Resultados: Trinta e oito pacientes foram randomizados: 20 no grupo budesonida e 18 no grupo placebo; 3 pacientes do grupo placebo não concluíram o tratamento. O grupo BAV apresentou melhora estatisticamente significativa evidenciada nos questionários NOSE e Lund-Kennedy, enquanto no SNOT observou-se melhora em ambos os grupos. Não houve diferença estatisticamente significativa na comparação entre os grupos em nenhum parâmetro. Entretanto, o grupo BAV mostrou uma redução maior da obstrução nasal (NOSE), comparado ao grupo PLA, cuja análise dos dados apresentou uma tendência para significância estatística (p=0,0593) que poderia ter sido evidenciada caso houvesse um tamanho amostral maior. Pacientes com doença respiratória exacerbada por aspirina no grupo BAV apresentaram melhora mais importante da obstrução nasal (NOSE) quando comparada ao placebo (p=0,0030). Não ocorreu aumento significativo dos eventos adversos após os tratamentos. Conclusão: A lavagem nasal com budesonida em alto volume de solução salina na rinossinusite crônica com polipose nasossinusal de difícil controle e asma brônquica não mostrou ser eficaz na melhora da qualidade de vida doença-específica para rinossinusite (SNOT-20) quando comparada ao placebo, mas uma tendência para melhora significativa da obstrução nasal (NOSE) foi observada / Introduction: Nasal irrigation with high-volume budesonide (HVB) in saline solution has been utilized in the treatment of chronic rhinosinusitis (CRS). Currently, there is no evidence of the superiority of HVB over placebo (PLA). The efficacy and safety of this treatment in patients with chronic rhinosinusitis with nasal polyposis (CRSwNP) and asthma still needs to be better established. Objective: This study evaluated the efficacy of nasal irrigation with HVB in patients with difficult-to-control CRS with nasal polyposis and bronchial asthma. Methods: Subjects were prospectively recruited and randomized into two groups: budesonide (1 mg/day) or placebo, diluted in 250 mL of 0.9% saline solution. Patients were instructed to irrigate each nostril with 125 mL of this solution every 12 hours for 12 weeks. Patients were evaluated for disease-specific quality of life (SNOT-20, NOSE) and underwent sinonasal endoscopy (Lund-Kennedy score) and an olfactory test (UPSIT). Adverse effects were evaluated by measurement of serum and urinary cortisol levels, assessment of lens opacity, and a water-drinking test for measurement of intraocular pressure. Results: Thirty-eight patients were randomized: 20 to the budesonide and 18 to the placebo group. Three patients in the placebo group did not complete treatment. The HVB group exhibited statistically significant improvement in NOSE and Lund-Kennedy scores, while improvement in NOSE scores was observed in both groups. There were no statistically significant differences in any parameter on between-group comparison. However, the HVB group exhibited a greater reduction in nasal obstruction scores (NOSE) as compared to the PLA group, with data analysis showing a trend toward statistical significance (p=0.0593) if the sample size had been larger. Patients with aspirin-exacerbated respiratory disease in the HVB group exhibited greater improvement in nasal obstruction (NOSE) than those in the placebo group (p=0.0030). There was no increase in adverse effects after treatment. Conclusion: In patients with difficult-to-control chronic rhinosinusitis with nasal polyposis and bronchial asthma, nasal irrigation with high-volume saline solution plus budesonide was not effective in improving disease-specific quality of life (SNOT-20) as compared with placebo, but was associated with a trend toward significant improvement in nasal obstruction (NOSE)

A rinite alérgica (RA) é a mais comum doença mediada por IgE, que afeta aproximadamente 500 milhões de pessoas em todo o mundo. A RA é a expressão clínica da ligação entre anticorpos do tipo IgE e antígenos na mucosa nasal resultando em inflamação. Estes anticorpos foram detectados na secreção nasal de pacientes com rinite alérgica. Na abordagem da doença, temos a imunoterapia específica (IT) como único tratamento imunomodulatório antígeno específico. Foi demonstrado que IT gera uma diminuição da resposta tardia ao alérgeno tanto na pele como na mucosa do trato respiratório e esta redução se correlaciona com diminuição no número de células infiltrando os tecidos e na quantidade de mediadores inflamatórios. Objetivo: Determinar a resposta local de IgE específica e IgG4 específica no lavado nasal de pacientes com rinite alérgica antes e após o tratamento com imunoterapia alérgeno específica para Dermatophagoides pteronyssinus por um período de 6 meses; determinar a resposta inflamatória padrão Th1/ Th2/ Th17 e avaliar escore de sintomas e contagem de células no lavado nasal. Método: Selecionamos pacientes sensibilizados ao Dermatophagoides pteronissinus com diagnóstico de rinite alérgica persistente. Realizamos as analises de sintomas nasais através da escala NIS e antes de iniciar o tratamento estes indivíduos realizaram provocação nasal com alérgeno e coleta de lavado nasal. Após 6 meses de tratamento IT e placebo estes pacientes foram reavaliados. Realizamos a analise de Imunoglobulinas (IgE especifica para Der p1 e 2, IgE total, e IgG4 especifica para Der p 1), contagem de células totais, citocinas padrão Th1/Th2 e Th17. Resultados: Analisamos 19 pacientes no grupo imunoterapia e 17 no grupo placebo. A avaliação dos sintomas pela escala NIS após 6 meses de intervenção, demonstrou diferença significativa nos grupos placebo e imunoterapia, em favor da IT. A concentração do extrato utilizado na provocação nasal foi maior no grupo imunoterapia após os 6 meses de tratamento mas sem significância estatística. Quanto a dosagem das imunoglobulinas observamos diminuição da IgE total após a intervenção assim como da contagem de células totais no lavado nasal. A dosagem das citocinas livres no lavado nasal não sofreram alterações significativas. Na provocação nasal observamos aumento de IL-13, IL-10 em ambos os grupos, independente da fase de tratamento. Conclusão: Não observamos nenhuma resposta local de IgE específica e IgG4 específica no lavado nasal de pacientes com rinite alérgica antes e após o tratamento com imunoterapia alérgeno específica para Dermatophagoides pteronyssinus por um período de 6 meses. Houve melhora no escore de sintomas e diminuição da IgE total e da contagem de células no lavado nasal / Allergic rhinitis (AR) is the most common disease mediated by IgE, affecting approximately 500 million people worldwide. The AR is the clinical expression of the link between the IgE-antibodies and antigens in the nasal mucosa resulting in inflammation. Such antibodies were detected in nasal secretions of allergic rhinitis patients. As treatment for this morbidity there is specific immunotherapy (IT) as only immunomodulatory specific antigen approach. It was demonstrated that IT generates a decrease in the late response to the allergen both in the skin and in the mucosa of the respiratory tract and this reduction correlates with the decrease in the number of infiltrating cells and in the amount of inflammatory mediators. Objective: To determine the local response of specific IgE and IgG4 in nasal lavage fluids of patients with allergic rhinitis before and after treatment with specific allergen immunotherapy to house dust mite for a period of 6 months; determine the standard inflammatory response of Th1 / Th2 / Th17 and evaluate symptom score and cell counts in nasal lavage. Method: We selected patients sensitized to Dermatophagoides pteronissinus diagnosed with persistent allergic rhinitis. Nasal symptoms were assessed by Nasal Index Score, and before treatment, allergen nasal challenge and collection of nasal lavage fluid were performed. After 6 months of treatment or placebo, the patients were reevaluated. IgE specific for Der p 1 and 2, total IgE and IgG4 specific for Der p 1, total cell count were determined as well as Th1 / Th2 and Th17 cytokines. Results: We analyzed 19 patients in the immunotherapy group and 17 in the placebo group. The evaluation of symptoms by NIS scale after 6 months of intervention showed significant differences in favor of the immunotherapy group. The concentration of the extract used in the nasal challenge was higher in the immunotherapy group after 6 months of treatment but without statistical significance. The total IgE decreased after the intervention as well as the total cell count in nasal lavage. The dosage of the free cytokines in nasal lavage fluid did not change significantly. In the nasal provocation we observe an increasing in IL-13 and IL-10 in both treatment groups. Conclusion: We observed no local changes in specific IgG4 or specific IgE response in nasal lavage fluid of patients with allergic rhinitis before and after treatment with specific allergen immunotherapy to house dust mite for a period of 6 months. There was an improvement in symptom scores and a decreased of total IgE and cell counts in nasal lavage

This thesis is dedicated to extracting expression robust features for 3D face recognition. The use of 3D imaging enables the extraction of discriminative features that can significantly improve the recognition performance due to the availability of facial surface information such as depth, surface normals and curvature. Expression robust analysis using information from both depth and surface normals is investigated by dividing the main facial region into patches of different scales. The nasal region and adjoining parts of the cheeks are utilized as they are more consistent over different expressions and are hard to deliberately occlude. In addition, in comparison with other parts of the face, these regions have a high potential to produce discriminative features for recognition and overcome pose variations. An overview and classification methodology of the widely used 3D face databases are first introduced to provide an appropriate reference for 3D face database selection. Using the FRGC and Bosphorus databases, a low complexity pattern rejector for expression robust 3D face recognition is proposed by matching curves on the nasal and its environs, which results in a low-dimension feature set of only 60 points. To extract discriminative features more locally, a novel multi-scale and multi-component local shape descriptor is further proposed, which achieves more competitive performances under the identification and verification scenarios. In contrast with many of the existing work on 3D face recognition that consider captures obtained with laser scanners or structured light, this thesis also investigates applications to reconstructed 3D captures from lower cost photometric stereo imaging systems that have applications in real-world situations. To this end, the performance of the expression robust face recognition algorithms developed for captures from laser scanners are further evaluated on the Photoface database, which contains naturalistic expression variations. To improve the recognition performance of all types of 3D captures, a universal landmarking algorithm is proposed that makes uses of different components of the surface normals. Using facial profile signatures and thresholded surface normal maps, facial roll and yaw rotations are calibrated and five main landmarks are robustly detected on the well-aligned 3D nasal region. The landmarking results show that the detected landmarks demonstrate high within-class consistency and can achieve good recognition performances under different expressions. This is also the first landmarking work specifically developed for the reconstructed 3D captures from photometric stereo imaging systems.

Orientador: Ercy Mara Cipulo Ramos / Banca: Dionei Ramos / Banca: Renata Calciolari Rossi e Silva / Resumo: Introdução: Apesar das rigorosas campanhas contra o fumo em muitos países, estimase que 1,25 bilhões de adultos sejam tabagistas e a projeção é de uma nova epidemia que pode levar a 1 bilhão de mortes tabaco-relacionadas durante o século 21. Os danos causados pelo tabagismo afetam principalmente o sistema respiratório, entretanto, também é considerado um importante fator de risco para doenças cardiovasculares. Sabe-se que a intensidade do fumo e sua cronicidade contribuem para um agravamento dos prejuízos causados pelo tabagismo, e que a cessação do tabagismo torna-se um marco crucial para evitar tais progressões assim como para reduzir a morbimortalidade por doenças tabaco-relacionadas. Objetivos: Esta dissertação teve como objetivos: avaliar o efeito da exposição aguda ao fumo na modulação autonômica de tabagistas adultos e investigar a influência da condição tabagística e da idade nesta resposta, além de avaliar o efeito da cessação tabagística no transporte mucociliar e na frequência de exacerbações em tabagistas com doença pulmonar obstrutiva crônica (DPOC)... / Abstract: Introduction: Despite stricter antismoking campaigns in several countries, is estimated to 1.25 billion adults are smokers and the projection is a new epidemic that may lead to 1 billion tobacco-related deaths during the 21st century. Damages caused by smoking mainly affect the respiratory system, however, it is also considered an important risk factor for cardiovascular disease. It is known that the smoking intensity and its chronicity contribute to a worsening of impairment caused by smoking, and that smoking cessation becomes a crucial milestone to avoid these progressions as well as to reduce morbimortality due to tobacco-related diseases. Aims: This Master's thesis aimed to evaluate the acute smoke exposure effect in the autonomic modulation of adult smokers and to investigate if the smoking status and age influence in this response, and to evaluate the smoking cessation effect on mucociliary clearance and in exacerbation frequency of smokers with chronic obstructive pulmonary disease (COPD). Methods: For the first aim, we evaluated heart rate variability (HRV) of adults smokers, participants of the smoking cessation program at FCT/UNESP, in smoke and recovery from this exposure moments (30 minutes after smoking)... / Mestre

Introdução: A lavagem nasal com budesonida em solução salina de alto volume (BAV) tem sido utilizada no tratamento de rinossinusite crônica (RSC). Atualmente, não existem evidências de superioridade da BAV sobre o placebo (PLA). Objetivo: O estudo avalia a eficácia da lavagem nasal com BAV na RSC com polipose nasossinusal de difícil controle e asma brônquica. Métodos: Os indivíduos foram prospectivamente recrutados e randomizados em dois grupos: budesonida (1mg/dia) ou placebo, diluídos em 250mL de Soro Fisiológico a 0,9%, e orientados para aplicar 125mL dessa solução em cada narina de 12 em 12 horas, por 12 semanas. Os pacientes foram avaliados quanto a: qualidade de vida doença-específica (SNOT-20, NOSE), endoscopia nasossinusal (Lund-Kennedy) e olfato (UPSIT). Efeitos adversos foram avaliados por meio do cortisol sérico e urinário, feita a avaliação da opacidade do cristalino e teste de sobrecarga hídrica para aferição da pressão ocular. Resultados: Trinta e oito pacientes foram randomizados: 20 no grupo budesonida e 18 no grupo placebo; 3 pacientes do grupo placebo não concluíram o tratamento. O grupo BAV apresentou melhora estatisticamente significativa evidenciada nos questionários NOSE e Lund-Kennedy, enquanto no SNOT observou-se melhora em ambos os grupos. Não houve diferença estatisticamente significativa na comparação entre os grupos em nenhum parâmetro. Entretanto, o grupo BAV mostrou uma redução maior da obstrução nasal (NOSE), comparado ao grupo PLA, cuja análise dos dados apresentou uma tendência para significância estatística (p=0,0593) que poderia ter sido evidenciada caso houvesse um tamanho amostral maior. Pacientes com doença respiratória exacerbada por aspirina no grupo BAV apresentaram melhora mais importante da obstrução nasal (NOSE) quando comparada ao placebo (p=0,0030). Não ocorreu aumento significativo dos eventos adversos após os tratamentos. Conclusão: A lavagem nasal com budesonida em alto volume de solução salina na rinossinusite crônica com polipose nasossinusal de difícil controle e asma brônquica não mostrou ser eficaz na melhora da qualidade de vida doença-específica para rinossinusite (SNOT-20) quando comparada ao placebo, mas uma tendência para melhora significativa da obstrução nasal (NOSE) foi observada / Introduction: Nasal irrigation with high-volume budesonide (HVB) in saline solution has been utilized in the treatment of chronic rhinosinusitis (CRS). Currently, there is no evidence of the superiority of HVB over placebo (PLA). The efficacy and safety of this treatment in patients with chronic rhinosinusitis with nasal polyposis (CRSwNP) and asthma still needs to be better established. Objective: This study evaluated the efficacy of nasal irrigation with HVB in patients with difficult-to-control CRS with nasal polyposis and bronchial asthma. Methods: Subjects were prospectively recruited and randomized into two groups: budesonide (1 mg/day) or placebo, diluted in 250 mL of 0.9% saline solution. Patients were instructed to irrigate each nostril with 125 mL of this solution every 12 hours for 12 weeks. Patients were evaluated for disease-specific quality of life (SNOT-20, NOSE) and underwent sinonasal endoscopy (Lund-Kennedy score) and an olfactory test (UPSIT). Adverse effects were evaluated by measurement of serum and urinary cortisol levels, assessment of lens opacity, and a water-drinking test for measurement of intraocular pressure. Results: Thirty-eight patients were randomized: 20 to the budesonide and 18 to the placebo group. Three patients in the placebo group did not complete treatment. The HVB group exhibited statistically significant improvement in NOSE and Lund-Kennedy scores, while improvement in NOSE scores was observed in both groups. There were no statistically significant differences in any parameter on between-group comparison. However, the HVB group exhibited a greater reduction in nasal obstruction scores (NOSE) as compared to the PLA group, with data analysis showing a trend toward statistical significance (p=0.0593) if the sample size had been larger. Patients with aspirin-exacerbated respiratory disease in the HVB group exhibited greater improvement in nasal obstruction (NOSE) than those in the placebo group (p=0.0030). There was no increase in adverse effects after treatment. Conclusion: In patients with difficult-to-control chronic rhinosinusitis with nasal polyposis and bronchial asthma, nasal irrigation with high-volume saline solution plus budesonide was not effective in improving disease-specific quality of life (SNOT-20) as compared with placebo, but was associated with a trend toward significant improvement in nasal obstruction (NOSE)

Introdução: O efeito da redução cirúrgica dos cornetos inferiores durante a rinosseptoplastia não é conhecido. São escassos os estudos que avaliaram os resultados de rinosseptoplastia através de instrumentos de qualidade de vida. Objetivo principal: Avaliar o efeito da redução cirúrgica dos cornetos inferiores sobre a qualidade de vida e sobre medidas de rinometria acústica de pacientes submetidos a rinosseptoplastia primária. Objetivos secundários: 1) Correlacionar as medidas objetivas de área da cavidade nasal aferidas por rinometria acústica com medidas subjetivas de qualidade de vida relacionadas à obstrução nasal; e 2) Avaliar os resultados cirúrgicos de pacientes submetidos à cirurgia da ponta nasal usando técnica de divisão vertical do domus utilizando escalas de qualidade de vida específicas. Delineamento: Ensaio clínico randomizado. População: Foram incluídos indivíduos com idade maior ou igual a 16 anos com obstrução nasal, candidatos a rinosseptoplastia primária funcional e estética. Intervenção: Rinosseptoplastia com ou sem redução dos cornetos inferiores. Desfechos: Mudança relativa [(escore pós-operatório – escore pré-operatório)/escore préoperatório] nos seguintes instrumentos: escore de qualidade de vida específico para obstrução nasal, com o Nasal Obstruction Symptom Evaluation na língua portugesa (NOSE-p); Rhinoplasty Outcomes Evaluation (ROE), específico para avaliação de resultados em rinoplastia; escore de qualidade de vida geral, World Health Organization Quality of Life Instrument-bref (WHOQOL-breve); escalas análogo-visuais para obstrução nasal (EAV); e medidas de área da cavidade nasal aferidas por rinometria acústica. Os desfechos foram avaliados aos 3 meses pós-operatórios, de forma cegada. Resultados: Foram incluídos 50 pacientes, predominantemente caucasianos com rinite alérgica moderada/severa. A média da idade foi 32 ± 12 anos, e 58% eram mulheres. A rinosseptoplastia esteve associada a melhora da qualidade de vida geral e específica, independentemente da realização ou não de cirurgia nos cornetos inferiores (P < 0,001). Não houve diferença entre os grupos nos escores NOSE-p (-75 vs. -73%; P = 0,893), em todos os domínios do WHOQOL-breve (P > 0,05) e nas medidas de rinometria acústica (P > 0,05). Na análise multivariada, após ajuste para uso de corticoide e fratura nasal prévia, não houve modificação desses resultados. O uso de corticosteroide tópico no terceiro mês pós-operatório foi menos prevalente entre os pacientes submetidos à redução cirúrgica dos cornetos inferiores quando comparado ao grupo controle [6 (24%) vs. 13 (54%), P = 0,03]. Não houve correlação entre os escores do questionário NOSE-p e as medidas de rinometria acústica (ρ = 0,054-0,247; P > 0.05). Entre os pacientes submetidos a divisão vertical do domus, a avaliação pós-operatória demonstrou melhora significativa dos escores médios nas escalas ROE, NOSE-p e EAV (76 ± 17, 23 ± 18 e 78 ± 21) quando comparados aos escores pré-operatórios (30 ± 17, 74 ± 21 e 20 ± 24, respectivamente; P < 0.001). Conclusão: 1) A redução cirúrgica dos cornetos inferiores durante a rinosseptoplastia não esteve associada a incremento nas medidas de qualidade de vida geral e específica e de rinometria acústica; a menor a necessidade de uso de corticosteroide tópico pós-operatório observada após essa intervenção deve ser confirmada em futuros estudos com maior seguimento. 2) As dimensões da cavidade nasal não estão correlacionadas a medidas de qualidade de vida específicas para obstrução nasal e provavelmente estimam aspectos diferentes da via aérea nasal. 3) A técnica de divisão vertical do domus para cirurgia da ponta nasal esteve associada a melhora em desfechos de qualidade de vida em curto prazo. / Introduction: The effects of inferior turbinate reduction during rhinoseptoplasty are unknown. Data evaluating the results of rhinoseptoplasty through quality of life outcomes are scarce. Main objective: To evaluate the effects of inferior turbinate reduction during primary rhinoseptoplasty on quality-of-life outcomes and nasal airway cross-sectional area. Secondary objectives: 1) To correlate objective measures of nasal cavity area, as measured through acoustic rhinometry, with subjective measures of quality of life related to nasal obstruction; and 2) To assess surgical outcomes of patients who underwent vertical division of domus for nasal tip refinement using specific quality of life instruments. Design: Randomized clinical trial. Subjects: Individuals over 16yr with nasal obstruction, eligible to functional and aesthetic rhinoseptoplasty. Intervention: Rhinoseptoplasty with or without inferior turbinate reduction. Outcomes: Relative change ([postoperative – preoperative] / preoperative score) on the following instruments: Nasal Obstruction Symptom Evaluation in the Portuguese language (NOSE-p), a quality-of-life instrument specifically related with nasal obstruction symptoms; Rhinoplasty Outcomes Evaluation (ROE), specifically designed to assess rhinoplasty results; a general quality-of-life instrument, World Health Organization Quality of Life Instrument-bref (WHOQOL-bref); nasal obstruction visual analogue scales; and nasal area measurements in acoustic rhinometry. Outcomes were blindly assessed 3 months postoperatively. Results: 50 patients were included, mainly Caucasians with moderate/severe allergic rhinitis symptoms. Mean age was 32 ± 12 yr, and 58% were female. Rhinoseptoplasty improved specific and general quality-of-life scores, irrespective of inferior turbinate surgery (P < 0.001). There was no difference between subjects submitted or not to turbinate reduction in NOSE-p scores (-75% vs. -73%; P = 0.893), in any of the WHOQOL-bref score domains (P > 0.05), and in acoustic rhinometry recordings (P > 0.05). Multivariable analysis, adjusted for postoperative topical corticosteroid use and previous nasal fracture, had no effect on these results. Fewer patients in the inferior turbinate reduction group were using topical corticosteroids 3 months after surgery (6 [24%] vs. 13 [54%], P = 0.03). There was no significant correlation between NOSE-p scores and acoustic rhinometry recordings (ρ = 0.054-0.247; P > 0.05). Among patients undergoing vertical dome division (n=44), mean postoperative ROE, NOSE-p and VAS scores improved significantly in postoperative evaluation (76 ± 17, 23 ± 18 and 78 ± 21) when compared to preoperative scores (30 ± 17, 74 ± 21 and 20 ± 24 respectively; P < 0.001). Conclusion: 1) Turbinate reduction during primary rhinoseptoplasty did not improve short-term general and specific quality-of-life outcomes and acoustic rhinometry recordings; the role of turbinate reduction in sparing chronic corticosteroid use should be confirmed in long-term follow-up studies. 2) The size of the nasal cavity and quality-of-life scores are not correlated and these measures may assess different aspects of the nasal airway. 3) Vertical dome division for nasal tip refinement resulted in short-term significant improvement of specific quality-of-life outcomes.

Introduction. The adverse health effects of cigarette smoking are well established, including the direct effects of nicotine on human endothelial cells and fibroblasts. However, the direct effects of nicotine in the nasal cavity remain uninvestigated. The study aim was to ascertain the direct effect of chemical components in cigarette smoke on the microbial flora or microbiota of the nasal cavity. Methods. We enrolled 40 participants from the Benson Idahosa University’s Health clinics to conduct this study. Information on demographic characteristics including age, sex, and smoking duration was obtained at baseline. We collected nasal swabs of 20 smokers and 20 non-smokers. The wool content of the swap stick was immediately stored in mac Cathy bottles containing 9 ml of normal saline and transported to the laboratory in less than 45 minutes after collection for microbiological analysis under aseptic condition. The enumeration of the microorganisms was carried out using the streak and pours plate method on Nutrient agar, Blood agar, Chocolate agar, Mac coney agar and Potato Dextrose agar (PDA). A two-sample t-test was used to determine differences in enumeration of microorganisms and isolates between smokers and non-smokers. Results. Total bacterial counts for the smokers ranged from 177 - 307 x 102 cfu/ml and 223 - 551 x 102 cfu/ml for non-smokers with (p = 0.046 Nutrient agar, and p = 0.011 PDA). The bacteria isolates were identified as Staphylococcus aureus, Escherichia coli, Klebsiella pneumonia, Proteus vulgaris and Streptococcus pneumonia, and the fungi isolates were identified as Aspergillus niger, Rhizopus stolonifer, Tricoderma viridae, respectively. The mean of nutrient agar in smokers is significantly lower (12.10) than that in nonsmokers (19.35), and the mean of PDA in smokers is significantly higher in smokers (5.75) than in nonsmokers (2.35). Higher percentages of gram-negative rods including Klebsiella pneumoniae (20%), Escherichia coli (20%) and Proteus vulgaris (20%) were identified in the smokers, which is in contrast to higher percentage of gram-positive cocci including Staphylococcus aureus and Streptococcus pneumonia identified in non-smokers. The most commonly isolated fungus in smokers was Aspergillus niger (45%) and nonsmokers was Rhizopus stolonifer (60%). Conclusions. Study findings demonstrated increased bacterial count and isolates in nasal cavity of smokers than non-smokers. Future studies should be warranted to understand the mechanistic role of nicotine in influencing microbiota of the nasal cavity.

Nasal sprays used for the treatment of cold and allergy symptoms use same device and formulation in children and adults. Owing to the obvious differences in nasal cavity dimensions between adults and children, the performance of nasal sprays products in children needs to be critically assessed. In an effort to evaluate the deposition patterns of nasal sprays administered to children, a nasal cast based on MRI images obtained from a 12-year-old child’s nasal cavity was developed using 3D printing technology. Glycerin-water mixtures providing sprays with a range of plume angles (26° - 62°), along with three additional commercial nasal sprays, were investigated by actuating the device into the cast under controlled conditions. Following spray administration, the cast was disassembled and subjected to image analysis followed by quantification of formulation deposition in each section of the cast using both chemical and image analysis. The results showed that nasal sprays impacted entirely in the anterior region of the 12-year-old child’s nasal cavity and limited amount of spray entered the turbinate region – the effect site for most topical drugs. Additional experiments were conducted to measure the deposition patterns of nasal sprays in the presence of a mucus layer on the surface of the nasal cast. In an effort to make the nasal deposition studies more relevant to human nasal conditions, the mucus coated nasal cast was tilted in order to induce a physical movement of the mucus layer from the anterior region to the nasopharynx. The presence of mucus did not result in a significant increase in the turbinate region deposition but tilting of the mucus coated nasal cast resulted in 20% - 40% deposition in the turbinate region, improving the posterior region deposition of sprays. Even with the enhanced posterior movement nearly 60% of the spray formulations remained in the anterior region, a site with poor absorption characteristics. The computational fluid dynamic simulations evaluated the impact of multiple parameters including plume angle, droplet diameter and administration conditions on the deposition of nasal sprays in the 12-year-old child’s nasal cavity. The simulations showed significant anterior deposition for all plume angles (10° – 50°) and droplet diameters (30 µm – 400 µm) tested, similar to the observations from the in vitro experiments. An additional parameter, the direction of nasal spray actuation in the nasal cavity, was identified as a critical factor improving the turbinate region deposition of sprays in the 12-year-old child’s nasal cavity in spite of the narrow nasal valve region.

Pre-systemic elimination by local enzymatic degradation can play a key role in limiting the bioavailability of intranasally administered drugs. Despite remarkable advancement in the characterization of the nasal biotransformative enzymes, knowledge of the role of the nasal mucosa in limiting bioavailability of therapeutic agents is still inadequate. The aim of this work was to evaluate the expression and substrate biotransformation activity of cytochrome P450 enzymes in the nasal mucosa using bovine olfactory and respiratory explants as in vitro models. Gene expression and localization of major CYP450 isoforms in the nasal mucosa were examined using RT-PCR and immunohistochemistry. The bovine nasal mucosa showed abundant expression of CYP2A6 and 3A4 genes whereas 1A1, 1A2, 2C9, and 2C19 isoforms were expressed at much lower levels. The CYP450 proteins were observed to be present in the epithelial layer and in submucosal glandular cells. The diffusion of melatonin, a CYP1A2 substrate, and the appearance of 6-hydroxymelatonin, its primary metabolite, across bovine olfactory and respiratory explants was measured, and nasal olfactory and respiratory microsomal preparations were used to quantify the kinetic parameters for melatonin 6-hydroxylation. Results indicated that bovine olfactory and respiratory CYP450 isoforms were metabolically active towards melatonin metabolism, and the respiratory mucosa demonstrated the greatest melatonin 6-hydroxylation activity. Numerical simulations were used to probe the effects of the relative magnitudes of the permeability coefficient and enzymatic parameters on net substrate mass transfer across nasal mucosal tissues. The simulations indicated that the concentration gradient of the drug coupled with its permeability coefficient were the most significant factors controlling the transport of drugs across the mucosal tissue. Enzymatic degradation decreased the flux of drugs across the mucosa and had the greatest impact on low permeability compounds. The results from these studies show that the bovine nasal mucosa possesses significant metabolic activity, and the flux of a metabolically labile substrate across the nasal mucosa can be significantly reduced by its enzymatic degradation within the tissue. Use of kinetic modeling to characterize of the extent of biotransformation in the nasal mucosa enables the identification of metabolism-limited bioavailability of intranasally administered drug compounds.